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Infection and Immunity, February 2001, p. 1151-1159, Vol. 69, No. 2
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.2.1151-1159.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

The Common Vaccine Adjuvant Aluminum Hydroxide Up-Regulates Accessory Properties of Human Monocytes via an Interleukin-4-Dependent Mechanism

Marina Ulanova,1,* Andrej Tarkowski,2 Mirjana Hahn-Zoric,1 and Lars Å. Hanson1

Departments of Clinical Immunology1 and Rheumatology,2 Göteborg University, S-41346 Göteborg, Sweden

Received 8 September 2000/Returned for modification 19 October 2000/Accepted 7 November 2000

Aluminum adjuvants are widely used in human vaccines based on their ability to enhance antibody production. However, the mechanisms underlying these effects remain unknown. In the present study we assessed the direct in vitro effect of aluminum hydroxide on human peripheral blood monocytes, specifically with regard to its impact on the phenotype and functional properties of this cell population. Our results revealed significant changes in the accessory properties of monocytes following short-term exposure of cultured cells to aluminum hydroxide. Thus, flow cytometry analyses showed an increase in the expression of major histocompatibility complex (MHC) class II, CD40, CD54, CD58, CD83, and CD86 molecules on the monocytes. In addition, many cells in the cultures containing aluminum hydroxide acquired typical dendritic morphology. Increased synthesis of interleukin-4 (IL-4) mRNA, but not gamma interferon mRNA, was also noted after exposure to aluminum hydroxide. The increase in cell surface expression of MHC class II did not occur in the presence of neutralizing IL-4 antibody or in cultures of highly purified monocytes or CD4-depleted mononuclear cells. Our findings suggest that aluminum hydroxide directly stimulates monocytes to produce proinflammatory cytokines activating T cells. Activated Th2 cells release IL-4, which in turn can induce an increase in the expression of MHC class II molecules on monocytes. The increase in the expression of antigen-presenting and costimulatory molecules leads to enhanced accessory functions of monocytes. These properties of aluminum hydroxide observed in vitro may explain its potent in vivo adjuvant effect.

* Corresponding author. Present address: Pulmonary Research Group, Room 574, HMRC, University of Alberta, Edmonton, Alberta, Canada T6G 2S2. Phone: (780) 492-1909. Fax: (780) 492-5329. E-mail: marina.ulanova{at}immuno.gu.se.

Infection and Immunity, February 2001, p. 1151-1159, Vol. 69, No. 2
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.2.1151-1159.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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